Effisayil 1 is the first multinational, randomized, double-blind, placebo-controlled, phase II trial to show promising clinical outcomes of spesolimab, a humanized monoclonal antibody targeting the IL-36 receptor, in patients presenting with a GPP flare. |
Effisayil 1 has a study design that evaluates the efficacy and safety of spesolimab more accurately; the study also includes more diverse populations and the largest sample size to date, as well as GPP-specific primary and key secondary endpoints. |
The IL-36 family plays a dominant role in the pathogenesis of GPP. |
Introduction
Effisayil 1 Study
Score | Short descriptor | Detailed descriptor |
---|---|---|
0 | Clear | Normal or post-inflammatory hyperpigmentation (erythema); no visible pustules; no scaling or crusting |
1 | Almost clear | Faint, diffuse pink or slightly red (erythema); low density and occasional small discrete pustules (non-coalescent); superficial focal scaling or crusting restricted to periphery of lesions |
2 | Mild | Light red (erythema); moderate-density grouped discrete small pustules (non-coalescent); predominantly fine scaling or crusting |
3 | Moderate | Bright red (erythema); high-density pustules with some coalescence; moderate scaling or crusting covering most or all lesions |
4 | Severe | Deep fiery red (erythema); very high-density pustules with pustular lakes; severe scaling or crusting covering most or all lesions |
Clinical Trials of Other Biologic Agents in Patients with GPP
TNF-α Inhibitor
Biologic agent | Study design | Population | Endpoints | Clinical outcomes |
---|---|---|---|---|
IL-36 receptor inhibitor | ||||
Spesolimab | Multicenter, randomized, double-blind, placebo-controlled, phase II trial Single dose 900 mg, i.v. Patients with a GPP flare received spesolimab or placebo on day 1, followed by an open-label dose/rescue therapy of spesolimab on day 8/after day 8, or both, and were followed to week 12 | Patients from Europe, North America, North Africa, and Asia (N = 53) Mean ± SD age (years): 43.2 ± 12.1 in spesolimab group, 42.6 ± 8.4 in placebo group | Primary endpoint: GPPGA pustulation subscore of 0 at week 1 Key secondary endpoint: GPPGA total score of 0 or 1 at week 1 | 54% (19/35) of patients in spesolimab group versus 6% (1/18) in placebo group achieved the primary endpoint 43% (15/35) of patients in spesolimab group versus 11% (2/18) in placebo group achieved the key secondary endpoint Acceptable safety profile Common AEs (week 1): pyrexia (spesolimab group versus placebo group: 6% versus 22%); dizziness (11% in the placebo group) |
TNF-α inhibitor | ||||
Adalimumab | Open-label, multicenter, single-arm, phase III, 52-week trial Dose 80 mg, s.c. Treatment at week 0, then 40 mg every 2 weeks until week 50 | Japanese patients with GPP (N = 10) Mean ± SD age (years): 49.8 ± 13.3 | Primary endpoint: CR (remission or improvement from baseline) at week 16 Secondary endpoints included improvements in PASI response rates and DLQI through 52 weeks | 7/10 patients achieved CR at week 16, and 5 patients achieved CR at week 52 Acceptable safety profile Most common AEs (52 weeks): nasopharyngitis, pruritus, and hypoalbuminemia |
IL-17/IL-17 receptor inhibitors | ||||
Secukinumab | Open-label, multicenter, single-arm, phase III, 52-week trial Dose 150 mg, s.c. Once per week at week 0, 1, 2, 3, and 4, and then every 4 weeks until week 52 | Japanese patients with GPP (N = 12) Mean ± SD age (years): 56.3 ± 15.33 | Primary endpoint: improvement in CGI at week 16 Secondary endpoints included improvements in the JDA total score, JDA component scores, and PASI scores at week 52 | 10/12 patients achieved the primary endpoint Efficacy of secukinumab was sustained until week 52 Acceptable safety profile Most common AEs (52 weeks): nasopharyngitis, urticaria, diabetes mellitus, and arthralgia |
Brodalumab | Open-label, multicenter, single-arm, phase III, 52-week trial Dose 140 mg, s.c. Treatment at day 1, week 1, and week 2, and then every 2 weeks until week 52 | Japanese patients with GPP (N = 12) or psoriatic erythroderma (N = 18) Mean ± SD age (years): 43.1 ± 16.8 | Primary endpoint: CGI remission or improvement Secondary endpoints included improvements in PASI scores and the Pustular Symptom Score through 52 weeks | 11/12 patients with GPP had CGI remission or improvement Favorable safety profile Most common AE (52 weeks): nasopharyngitis |
Ixekizumab | Open-label, multicenter, single-arm, phase III, 52-week trial Administrated at week 0 (dose 160 mg), week 2–12 (80 mg every 2 weeks), and week 16–52 (80 mg every 4 weeks), s.c | Japanese patients with plaque psoriasis (N = 78), erythrodermic psoriasis (N = 8), and GPP (N = 5) Mean ± SD age (years): 48.2 ± 15.6 | Key endpoints included improvements in PASI scores, sPGA, and global improvement scores | All five patients with GPP had resolved or improved symptoms Most common treatment-emergent AEs (52 weeks): nasopharyngitis, eczema, seborrheic dermatitis, urticaria, and injection site reactions |
IL-23 inhibitor | ||||
Guselkumab | Open-label, multicenter, single-arm, phase III, 52-week trial Dose 50 mg, s.c. Treatment at week 0 and 4, and then every 8 weeks until week 52 | Japanese patients with GPP (N = 10) or erythrodermic psoriasis (N = 11) Mean ± SD age (years): 42.6 ± 8.97 | Primary endpoint: improvement in CGI score at week 16 Secondary endpoints included improvements in PASI, JDA severity index total score, and IGA score through 52 weeks | 7/9 patients achieved the primary endpoint Treatment effect of guselkumab was observed within 1 week after treatment in 50% (5/10) of patients Favorable safety profile Most common treatment-emergent AE (52 weeks): nasopharyngitis |